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Background: Epilepsy and other seizure disorders account for a high disease burden in Germany. As a timely diagnosis and accurate treatment are crucial, improving the management of these disorders is important. Outside of Germany, outpatient long-term video EEGs (ALVEEGs) have demonstrated the potential to support the diagnosis and management of epilepsy and other seizure disorders. This study aims to evaluate the implementation of ALVEEGs as a new diagnostic pathway in eastern parts of Germany to diagnose epilepsy and other seizure disorders and to assess if ALVEEGs are equally effective as the current inpatient-monitoring gold standard, which is currently only available at a limited number of specialized centers in Germany. Methods: ALVEEG is a prospective, multicenter, randomized controlled equivalence trial, involving five epilepsy centers in the eastern states of Germany. Patients will be randomized into either intervention (IG) or control group (CG), using a permuted block randomization. The sample size targeted is 688 patients, continuously recruited over the trial. The IG will complete an ALVEEG in a home setting, including getting access to a smartphone app to document seizure activity. The CG will receive care as usual, i.e., inpatient long-term video-EEG monitoring. The primary outcome is the proportion of clinical questions being solved in the IG compared to the CG. Secondary outcomes include hospital stays, time until video EEG, time until diagnosis and result discussion, patients' health status, quality of life and health competence, and number and form of epilepsy-related events and epileptiform activity. Alongside the trial, a process implementation and health economic evaluation will be conducted. Discussion: The extensive evaluation of this study, including an implementation and health economic evaluation, will provide valuable information for health policy decision-makers to optimize future delivery of neurological care to patients affected by epilepsy and other seizure disorders and on the uptake of ALVEEG into standard care in Germany. Trial registration: German Clinical Trials Register (DRKS00032220), date registered: December 11, 2023. [ABSTRACT FROM AUTHOR]

Objective: In temporal lobe epilepsy (TLE), a taxonomy classifying patients into 3 cognitive phenotypes has been adopted: minimally, focally, or multidomain cognitively impaired (CI). We examined gray matter (GM) thickness patterns of cognitive phenotypes in drug‐resistant TLE and assessed potential use for predicting postsurgical cognitive outcomes. Methods: TLE patients undergoing presurgical evaluation were categorized into cognitive phenotypes. Network edge weights and distances were calculated using type III analysis of variance F‐statistics from comparisons of GM regions within each TLE cognitive phenotype and age‐ and sex‐matched healthy participants. In resected patients, logistic regression models (LRMs) based on network analysis results were used for prediction of postsurgical cognitive outcome. Results: A total of 124 patients (63 females, mean age ± standard deviation [SD] = 36.0 ± 12.0 years) and 117 healthy controls (63 females, mean age ± SD = 36.1 ± 12.0 years) were analyzed. In the multidomain CI group (n = 66, 53.2%), 28 GM regions were significantly thinner compared to healthy controls. Focally impaired patients (n = 37, 29.8%) showed 13 regions, whereas minimally impaired patients (n = 21, 16.9%) had 2 significantly thinner GM regions. Regions affected in both multidomain and focally impaired patients included the anterior cingulate cortex, medial prefrontal cortex, medial temporal, and lateral temporal regions. In 69 (35 females, mean age ± SD = 33.6 ± 18.0 years) patients who underwent surgery, LRMs based on network‐identified GM regions predicted postsurgical verbal memory worsening with a receiver operating curve area under the curve of 0.70 ± 0.15. Interpretation: A differential pattern of GM thickness can be found across different cognitive phenotypes in TLE. Including magnetic resonance imaging with clinical measures associated with cognitive profiles has potential in predicting postsurgical cognitive outcomes in drug‐resistant TLE. ANN NEUROL 2024;95:984–997 [ABSTRACT FROM AUTHOR]

Background and purpose: In patients with epilepsy and sustained seizure freedom, guidelines recommend considering discontinuation of antiseizure medication (ASM) based on shared decision‐making. This study aims to identify factors associated with non‐discontinuation of ASM in seizure‐free patients. Methods: Retrospective data from three sites of an academic outpatient clinic were analyzed. Adult patients with epilepsy who have been seizure‐free for ≥24 months on ASM monotherapy were included. The primary end‐point was non‐discontinuation of ASM, defined as no discontinuation or no dose reduction of ≥25% at the last outpatient clinic visit in the ultimate seizure‐free interval. Secondary end‐points included frequency of discussion on discontinuation attempts between patients and physicians, adherence to ASM discontinuation decisions, and post‐discontinuation seizure outcomes. Results: Out of 338 included patients, 81.7% did not discontinue ASM and did not reduce its dose, 11.5% discontinued ASM and 6.8% had a significant dose reduction. Factors independently associated with non‐discontinuation of ASM were history of focal to bilateral or generalized tonic–clonic seizures (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.08–5.06), history of breakthrough seizures (OR 3.32, 95% CI 1.10–10.04), history of failed attempts to discontinue or reduce the ASM dose (OR 4.67, 95% CI 1.03–21.11) and higher ASM load at the index visit (OR 6.10, 95% CI 2.09–17.78). Discontinuation attempts were made during the entire period of seizure freedom and were most commonly undertaken ≥10 years after the last seizure. Conclusions: This study provides insights into factors associated with the shared decision‐making process regarding ASM discontinuation in seizure‐free patients and highlights the importance of considering individual patient characteristics and seizure history. [ABSTRACT FROM AUTHOR]

Neuroinflammation is highly influenced by microglia, particularly through activation of the NLRP3 inflammasome and subsequent release of IL-1β. Extracellular ATP is a strong activator of NLRP3 by inducing K+ efflux as a key signaling event, suggesting that K+-permeable ion channels could have high therapeutic potential. In microglia, these include ATP-gated THIK-1 K+ channels and P2X7 receptors, but their interactions and potential therapeutic role in the human brain are unknown. Using a novel specific inhibitor of THIK-1 in combination with patch-clamp electrophysiology in slices of human neocortex, we found that THIK-1 generated the main tonic K+ conductance in microglia that sets the resting membrane potential. Extracellular ATP stimulated K+ efflux in a concentration-dependent manner only via P2X7 and metabotropic potentiation of THIK-1. We further demonstrated that activation of P2X7 was mandatory for ATP-evoked IL-1β release, which was strongly suppressed by blocking THIK-1. Surprisingly, THIK-1 contributed only marginally to the total K+ conductance in the presence of ATP, which was dominated by P2X7. This suggests a previously unknown, K+-independent mechanism of THIK-1 for NLRP3 activation. Nuclear sequencing revealed almost selective expression of THIK-1 in human brain microglia, while P2X7 had a much broader expression. Thus, inhibition of THIK-1 could be an effective and, in contrast to P2X7, microglia-specific therapeutic strategy to contain neuroinflammation. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy with generalized tonic–clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. Methods: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. Results: We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13–22) and a median follow‐up duration of 10 years (IQR = 5–20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2‐year remission was 24 months (IQR = 24–46.5) with a median number of 1 (IQR = 1–2) ASM. During the long‐term follow‐up (i.e., 202 patients followed ≥5‐years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no‐remission and relapsing–remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic–clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12‐month follow‐up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. Significance: GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations. [ABSTRACT FROM AUTHOR]

Background: The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and meta-analysis was to estimate the association between the extent of WML in CSVD and epilepsy, analyze whether these WML are associated with an increased risk of seizure recurrence, and evaluate if treatment with anti-seizure medication (ASM) is justified in first-seizure patients with WML and no cortical lesions. Methods: Following a pre-registered study protocol (PROSPERO-ID CRD42023390665), we systematically searched Pubmed and Embase for relevant literature comparing WML load between patients with epilepsy and controls as well as studies on seizure recurrence risk and ASM therapy in the presence vs. absence of WML. We calculated pooled estimates using a random effects model. Results: Eleven studies comprising 2983 patients were included in our study. Presence of WML (OR 2.14, 95% CI 1.38–3.33) and presence of relevant WML as assessed by visual rating scales (OR 3.96, 95% CI 2.55–6.16) but not WML volume (OR 1.30, 95% CI 0.91–1.85) were significantly associated with seizures. These results stayed robust in sensitivity analyses restricted to studies on patients with late-onset seizures/epilepsy. Only two studies assessed the association between WML and risk of seizure recurrence with conflicting results. Currently, there are no studies on the efficacy of ASM therapy in the presence of WML in CSVD. Conclusions: This meta-analysis suggests an association between presence of WML in CSVD and seizures. More research is needed addressing the association between WML and risk of seizure recurrence and ASM therapy focusing on a population of patients with a first unprovoked seizure. [ABSTRACT FROM AUTHOR]

Background: Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%. Methods: Inclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey. Results: Eleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%–16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8–69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0–9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate. Conclusions: Even in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment. [ABSTRACT FROM AUTHOR]

Background: Antiseizure medications can have negative effects on plasma lipid levels. Objectives: To evaluate plasma lipid changes in patients with newly diagnosed focal epilepsy treated with eslicarbazepine acetate (ESL) or controlled-release carbamazepine (CBZ-CR) monotherapy during a phase III, randomized, double-blind (DB) trial and 2 years of ESL treatment in an open-label extension (OLE). Design: Post hoc analysis of a phase III trial and OLE study. Methods: Proportions of patients with elevated levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were assessed at DB baseline, OLE baseline (last visit of DB trial), and end of OLE. Results: A total of 184 patients received ESL monotherapy during the OLE: 96 received ESL monotherapy in the DB trial and 88 patients received CBZ-CR monotherapy. The proportions of patients with elevated total cholesterol and LDL cholesterol increased significantly during the DB trial in those treated with CBZ-CR monotherapy [total cholesterol, +14.9% (p < 0.001); LDL cholesterol, +11.5% (p = 0.012)] but decreased significantly after switching to ESL monotherapy in the OLE [total cholesterol, −15.3% (p = 0.008); LDL cholesterol, −11.1% (p = 0.021)]. No significant changes were observed in those treated with ESL monotherapy during the DB trial and OLE. At the end of the DB trial, between-group differences (ESL–CBZ-CR) in the proportions of patients with elevated total and LDL cholesterol were −13.6% (p = 0.037) and −12.3% (p = 0.061), respectively; at the end of the OLE, these between-group differences were −6.0% (p = 0.360) and −0.6% (p = 1.000), respectively. Conclusion: A lower proportion of patients with newly diagnosed focal epilepsy had increased levels of total and LDL cholesterol, compared to baseline, following monotherapy with ESL versus CBZ-CR; after switching from CBZ-CR to ESL, the proportions of patients with increased levels decreased significantly. Registration: ClinicalTrials.gov NCT01162460/NCT02484001; EudraCT 2009-011135-13/2015-001243-36. Plain language summary The impact of treatment with either eslicarbazepine acetate or controlled-release carbamazepine on cholesterol levels in patients with newly diagnosed focal epilepsy Patients with epilepsy have an increased risk of having cardiovascular and cerebrovascular diseases (e.g., myocardial infarction and stroke). Treatment with antiseizure medications can have a negative effect on blood cholesterol levels [such as total cholesterol and low-density lipoprotein (LDL) cholesterol], which can further increase the risk of cardiovascular and cerebrovascular diseases. We examined the impact of monotherapy treatment (i.e., treatment with only one antiseizure medication) using either eslicarbazepine acetate (ESL) or a controlled-release formulation of carbamazepine (CBZ-CR) in 184 patients with newly diagnosed focal epilepsy (ESL, 96 patients; CBZ-CR, 88 patients). Patients received monotherapy with ESL or CBZ-CR for approximately 1 year in a phase III clinical trial. After this, the patients could continue into a 2-year extension study during which they all received monotherapy with ESL. We assessed the proportions of patients with elevated levels of total cholesterol and LDL cholesterol at the beginning and end of the phase III trial, and at the end of the extension study. At the beginning of the phase III trial, the proportions of patients with elevated total cholesterol and elevated LDL cholesterol were similar between treatment groups. During the phase III trial, the proportions of patients with elevated total cholesterol and elevated LDL cholesterol increased in those treated with CBZ-CR monotherapy (total cholesterol, +14.9%; LDL cholesterol, +11.5%) but decreased after switching to ESL monotherapy in the extension study (total cholesterol, −15.3%; LDL cholesterol, −11.1%). By contrast, the proportions of patients with elevated levels of total cholesterol and LDL cholesterol remained relatively stable in those treated with ESL monotherapy during the phase III trial and extension study. These findings indicate that ESL monotherapy may be an appropriate treatment option for patients with newly diagnosed focal epilepsy who either already have, or who are at risk of developing, high levels of cholesterol, since this may reduce their likelihood of having cardiovascular and cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Objective: To investigate cost in working hours for initial integration of interictal EEG source localization (ESL) into clinical practice of a tertiary epilepsy center, and to examine concordance of results obtained with three different ESL pipelines. Methods: This prospective study covered the first year of using ESL in the Epilepsy‐Center Berlin‐Brandenburg. Patients aged ≥14 years with drug‐resistant focal epilepsy referred for noninvasive presurgical evaluation were included. Interictal ESL was based on low‐density EEG and individual head models. Source maxima were obtained from two freely available software packages and one commercial provider. One physician and computer scientist documented their working hours for setting up and processing ESL. Additionally, a survey was conducted among epilepsy centers in Germany to assess the current role of ESL in presurgical evaluation. Results: Of 40 patients included, 22 (55%) had enough interictal spikes for ESL. The physician's working times decreased from median 4.7 hours [interquartile range 3.9‐6.4] in the first third of cases to 2.0 hours [1.9‐2.4] in the remaining two thirds; P < 0.01. In addition, computer scientist and physician spent a total of 35.5 and 33.0 working hours on setting up the digital infrastructure, and on training and testing. Sublobar agreement between all three pipelines was 20%, mean measurement of agreement (kappa) 0.13. Finally, the survey revealed that 53% of epilepsy centers in Germany currently use ESL for presurgical evaluation. Significance: This study provides information regarding expected effort and costs for integration of ESL into an epilepsy surgery program. Low result agreement across different ESL pipelines calls for further standardization. [ABSTRACT FROM AUTHOR]

Introduction: The increasing identification of specific autoantibodies against brain structures allows further refinement of the group of autoimmune-associated epilepsies and affects diagnostic and therapeutic algorithms. The early etiological allocation of a first seizure is particularly challenging, and the contribution of cerebrospinal fluid (CSF) analysis is not fully understood. Methods: In this retrospective study with a mean of 7.8 years follow-up involving 39 well-characterized patients with the initial diagnosis of new-onset seizure or epilepsy of unknown etiology and 24 controls, we determined the frequency of autoantibodies to brain proteins in CSF/serum pairs using cell-based assays and unbiased immunofluorescence staining of unfixed murine brain sections. Results: Autoantibodies were detected in the CSF of 30.8% of patients. Underlying antigens involved glial fibrillary acidic protein (GFAP) and N-methyl-D-aspartate (NMDA) receptors, but also a range of yet undetermined epitopes on neurons, glial and vascular cells. While antibody-positive patients had higher frequencies of cancer, they did not differ from antibody-negative patients with respect to seizure type, electroencephalography (EEG) and cranial magnetic resonance imaging (cMRI) findings, neuropsychiatric comorbidities or pre-existing autoimmune diseases. In 5.1% of patients with seizures or epilepsy of initially presumed unknown etiology, mostly CSF findings resulted in etiological reallocation as autoimmune-associated epilepy. Discussion: These findings strengthen the potential role for routine CSF analysis. Further studies are needed to understand the autoantibody contribution to etiologically unclear epilepsies, including determining the antigenic targets of underlying autoantibodies. [ABSTRACT FROM AUTHOR]

Objective: Many people with epilepsy report subjective cognitive impairment (SCI), i.e., problems with memory, attention, or executive functions, reducing quality of life. Nevertheless, overlap with objective cognitive impairment (OCI) is often weak. One reason may be a domain‐specific mismatch between subjective reports and objective tests. We aimed to evaluate relations between SCI and OCI of corresponding domains and to assess whether these differ between persons who over‐ or underestimate their performance. Methods: In this prospective, cross‐sectional sample of 104 adult inpatients with epilepsy, we performed multiple regression analyses predicting SCI in the domains attention, memory, and executive functions. We tested relationships with measures of psychomotor speed, short‐term memory, verbal learning, verbal delayed recall, and word fluency while controlling for age, sex, seizure frequency, structural lesions, mono‐ versus polytherapy and adverse events of antiseizure medication (ASM), depressive and anxiety symptoms, level of education, and employment status. Furthermore, we tested whether these relationships differed between realistic raters and over‐ and underestimators. Results: We found domain‐specific relations for attention and executive functions for the full sample, explaining a small proportion of variance of SCI (general dominance index =.03 and.004), whereas ASM adverse events and psychological variables were more important predictors. When dividing the sample according to the concordance of SCI and OCI, we found high frequencies of both over‐ (23%–46%) and underestimation (31%–35%) depending on the domain. The explanatory power of OCI for SCI was stronger within the subgroups compared to the full sample, suggesting nonlinear relationships and different underlying mechanisms for realistic raters, underestimators, and overestimators. Significance: Domain‐specific SCI and OCI are related, and both should be assessed with standardized instruments. These relationships differ between over‐ and underestimators as well as realistic raters. Based on the concordance of self‐ratings and objective measures, tailored counseling and treatment should be offered. [ABSTRACT FROM AUTHOR]

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The piriform cortex (PC) is located at the junction of the temporal and frontal lobes. It is involved physiologically in olfaction as well as memory and plays an important role in epilepsy. Its study at scale is held back by the absence of automatic segmentation methods on MRI. We devised a manual segmentation protocol for PC volumes, integrated those manually derived images into the Hammers Atlas Database (n = 30) and used an extensively validated method (multi‐atlas propagation with enhanced registration, MAPER) for automatic PC segmentation. We applied automated PC volumetry to patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE; n = 174 including n = 58 controls) and to the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 151, of whom with mild cognitive impairment (MCI), n = 71; Alzheimer's disease (AD), n = 33; controls, n = 47). In controls, mean PC volume was 485 mm3 on the right and 461 mm3 on the left. Automatic and manual segmentations overlapped with a Jaccard coefficient (intersection/union) of ~0.5 and a mean absolute volume difference of ~22 mm3 in healthy controls, ~0.40/ ~28 mm3 in patients with TLE, and ~ 0.34/~29 mm3 in patients with AD. In patients with TLE, PC atrophy lateralised to the side of hippocampal sclerosis (p <.001). In patients with MCI and AD, PC volumes were lower than those of controls bilaterally (p <.001). Overall, we have validated automatic PC volumetry in healthy controls and two types of pathology. The novel finding of early atrophy of PC at the stage of MCI possibly adds a novel biomarker. PC volumetry can now be applied at scale. [ABSTRACT FROM AUTHOR]

Objective: Many people with epilepsy (PWE) suffer from reduced everyday functioning such as unemployment, relationship difficulties, or lifestyle limitations. To identify whether subjective cognitive impairment (SCI) is a potential source of these impairments, associations with restrictions of daily life (RDL) and reduced daily activities (DA) were examined. Methods: In a prospective cross‐sectional sample of 316 adult in‐patients with epilepsy, multiple regression analyses were calculated predicting RDL and DA. The relationships between these two measures and SCI were controlled for age, sex, seizure frequency, presence of structural lesions, epilepsy duration, mono‐ vs polytherapy and adverse events of antiseizure medication (ASM), level of depressive and anxiety symptoms, education, and employment. We also checked for an interaction between depressive symptoms and SCI, to evaluate whether patients with more depressive symptoms are more vulnerable for unfavorable associations between SCI and RDL or DA, respectively. General dominance indices (GDIs) were calculated to compare predictors. Results: Substantial SCI was present in 46% of our sample. SCI was independently associated with RDL and DA. Comparison of relative predictor importance revealed that SCI accounted for 23% of the total variance of RDL (GDISCI = 0.12, RRDL2 = 50%) and 24% of the total variance of DA (GDISCI = 0.08, RDA2 = 32%). SCI was among the two most important predictors in both models. PWE with more depressive symptoms had stronger associations between SCI and RDL or DA, respectively. Significance: Subjective cognitive impairment represents a frequent concern in PWE and may have detrimental consequences for their everyday life. PWE with depressive symptoms may be at greater risk of unfavorable relationships between SCI and everyday functioning. Exchange and collaboration between professionals offering psychotherapeutic, neuropsychological, and psychosocial interventions are crucial to address the patients' individual needs. [ABSTRACT FROM AUTHOR]

Objective: Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC). Several studies suggest antiseizure effects also beyond these three epilepsy syndromes. Methods: In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with epilepsy at 16 epilepsy centers. Results: The study cohort comprised 311 patients with epilepsy with a median age of 11.3 (0‐72) years (235 children and adolescents, 76 adults). Therapy with CBD was off‐label in 91.3% of cases due to age, epilepsy subtype, lack of adjunct therapy with clobazam, and/or higher dose applied. CBD titration regimens were slower than recommended, with good tolerability of higher doses particularly in children. Of all patients, 36.9% experienced a reduction in seizure frequency of >50%, independent of their epilepsy subtype or clobazam co‐medication. The median observation period was 15.8 months. About one third of all patients discontinued therapy within the observation period due to adverse effects or lack of efficacy. Adverse effects were reported frequently (46.9%). Significance: Our study highlights that CBD has an antiseizure effect comparable to other antiseizure medications with a positive safety profile independent of the epilepsy subtype. Comedication with clobazam was not associated with a better outcome. Higher doses to achieve seizure frequency reduction were safe, particularly in children. These findings call for further trials for an extended approval of CBD for other epilepsy subtypes and for children <2 years of age. [ABSTRACT FROM AUTHOR]

Background: In patients with drug-resistant focal epilepsy, resective surgery is the most successful treatment option to achieve seizure freedom. However, a surprisingly high rate of patients declines their physicians' recommendation to undergo removal of the seizure focus or—if necessary—further video-EEG monitoring (VEM). Methods: In this prospective study, consecutive patients in presurgical assessment with at least one scalp VEM between 2016 and 2018 were included. We assessed both epilepsy-related and psychosocial variables as well as decision-making of physicians and patients, including reasons for decline in the latter. Results: Out of 116 patients with a total of 165 VEM, 20 patients were eventually found to be ineligible for resection, 51 declined, and 45 agreed on recommendations for resection or further VEM diagnostics. Patients most frequently declined due to general fear of brain surgery (n = 30, 59%) and currently lower seizure frequency (n = 11, 22%). An independent predictor of patients' decline was less epilepsy-related fear (OR 0.43; p = 0.02) assessed in a standardised questionnaire. Conclusion: Half of the patients potentially eligible for resective surgery decline the operation or further VEM procedures. Patients who decline are more fearful of brain surgery than of ongoing disabling seizures. More insight is needed to improve counselling of patients. [ABSTRACT FROM AUTHOR]

Objective: Identifying factors associated with surgical decision‐making is important to understand reasons for underutilization of epilepsy surgery. Neurologists' recommendations for surgery and patients' acceptance of these recommendations depend on clinical epilepsy variables, for example, lateralization and localization of seizure onset zones. Moreover, previous research shows associations with demographic factors, for example, age and sex. Here, we investigate the relevance of patients' psycho‐social profile for surgical decision‐making. Methods: We prospectively studied 296 patients from two large German epilepsy centers. Multiple logistic regression analyses were used to investigate variables linked to neurologists' recommendations for and patients' acceptance of surgery or intracranial video‐electroencephalographic monitoring. Patients' psycho‐social profiles were assessed via self‐reports and controlled for various clinical–demographic variables. Model selection was performed using the Akaike information criterion. Results: As expected, models for neurologists' surgery recommendations primarily revealed clinical factors such as lateralization and localization of the seizure onset zone, load with antiseizure medication (ASM), and site of the epilepsy‐center. For this outcome, employment was the only relevant psycho‐social aspect (odds ratio [OR] =.38, 95% confidence interval [CI] =.13–1.11). In contrast, three of the five relevant predictors for patients' acceptance were psycho‐social. Higher odds were found for those with more subjective ASM adverse events (OR = 1.04, 95% CI =.99–1.00), more subjective seizure severity (OR = 1.12, 95% CI = 1.01–1.24), and lower subjective cognitive impairment (OR =.98, 95% CI =.96–1.00). Significance: We demonstrated the relevance of the patients' psycho‐social profile for decision‐making in epilepsy surgery, particularly for patients' decisions. Thus, in addition to clinical–demographic variables, patients' individual psycho‐social characteristics add to the understanding of surgical decision‐making. From a clinical perspective, this calls for individually tailored counseling to assist patients in finding the optimal treatment option. [ABSTRACT FROM AUTHOR]

Background: Antiseizure medications can have negative effects on plasma lipid levels. Objectives: To evaluate plasma lipid changes in patients with newly diagnosed focal epilepsy treated with eslicarbazepine acetate (ESL) or controlled-release carbamazepine (CBZ-CR) monotherapy during a phase III, randomized, double-blind (DB) trial and 2 years of ESL treatment in an open-label extension (OLE). Design: Post hoc analysis of a phase III trial and OLE study. Methods: Proportions of patients with elevated levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were assessed at DB baseline, OLE baseline (last visit of DB trial), and end of OLE. Results: A total of 184 patients received ESL monotherapy during the OLE: 96 received ESL monotherapy in the DB trial and 88 patients received CBZ-CR monotherapy. The proportions of patients with elevated total cholesterol and LDL cholesterol increased significantly during the DB trial in those treated with CBZ-CR monotherapy [total cholesterol, +14.9% (p < 0.001); LDL cholesterol, +11.5% (p = 0.012)] but decreased significantly after switching to ESL monotherapy in the OLE [total cholesterol, -15.3% (p = 0.008); LDL cholesterol, -11.1% (p = 0.021)]. No significant changes were observed in those treated with ESL monotherapy during the DB trial and OLE. At the end of the DB trial, betweengroup differences (ESL--CBZ-CR) in the proportions of patients with elevated total and LDL cholesterol were -13.6% (p = 0.037) and -12.3% (p = 0.061), respectively; at the end of the OLE, these between-group differences were -6.0% (p = 0.360) and -0.6% (p = 1.000), respectively. Conclusion: A lower proportion of patients with newly diagnosed focal epilepsy had increased levels of total and LDL cholesterol, compared to baseline, following monotherapy with ESL versus CBZ-CR; after switching from CBZ-CR to ESL, the proportions of patients with increased levels decreased significantly. [ABSTRACT FROM AUTHOR]

Acute symptomatic seizures are often caused by acute structural brain lesions. However, German guidelines for driving eligibility do not cover this situation. Following an acute symptomatic seizure of structural etiology, the risk of later unprovoked seizures is as high as after an isolated unprovoked seizure (20–40% in 10 years). Hence, we suggest applying the same duration of observation without driving eligibility, i.e., 6 seizure-free months for private driving of passenger cars and 2 seizure-free years without antiseizure medication for busses, trucks, and professional driving. [ABSTRACT FROM AUTHOR]

With respect to epilepsy in old age, two groups of patients with different needs and challenges must be distinguished, which are also treated separately in this article: those who have grown old with epilepsy and those with epilepsy occurring for the first time in older age. Diagnostically, the first group is unproblematic as there are only relatively rarely patients with a misdiagnosis of epilepsy that has been maintained over decades. In contrast, epilepsy beginning in older age is more often misdiagnosed or diagnosed with a delay because of the often comparatively harmless semiology including nonconvulsive status epilepticus. Therapeutically, the question of switching from an "old" antiepileptic drug with negative effects on electrolytes, hormones, bone density, hepatic and vitamin metabolism as well as on cognitive parameters, such as alertness and memory, to a "modern" agent frequently arises. While many of these newer compounds offer benefits there are always surprises with unexpected, particularly psychiatric, adverse effects. If the patient has been seizure-free for a long time, the question of discontinuing or at least reducing the dose of antiepileptic drugs naturally arises. At the onset of epilepsy in old age, the selection of an antiepileptic drug, which usually needs to be taken for the rest of the patient's life, requires special consideration of individual aspects, not least because of the often numerous comorbidities and already existing medications. The aim of this article is to present the current state of knowledge and to assist in the care of older patients in the area of conflict between the limited evidence-based data and the necessity of a therapeutic decision in routine clinical practice. [ABSTRACT FROM AUTHOR]

Removal of the seizure focus, either by resection or by laser thermal ablation, has a high chance to result in seizure freedom in well-selected patients with focal drug-resistant epilepsy. Vagus nerve stimulation and deep brain stimulation are palliative approaches, which aim to reduce the number and severity of epileptic seizures. In older patients there seems to be an overall reluctance with respect to all epilepsy surgery procedures. In this context, "older" means patients with an age of 50 years and above. In this article, we assess if there are clinically relevant differences with respect to seizure outcome and complications in older patients compared to younger patients when using the different epilepsy surgery approaches. Overall, available and reliable data are sparse and there are hardly any studies of high quality. Most data with almost 700 patients are on resective surgery, predominantly from retrospective monocentric studies on temporal lobe epilepsy. In summary, it seems that the rates of seizure freedom and complications do not differ significantly in older patients compared to younger patients; however, it cannot be ruled out that in the group of older patients rather clear and straightforward cases have been resected. For thermal ablation procedures, no specific data on older patients exist. The minimally invasive approach with few complications, however, may be interesting particularly for older patients. With respect to vagus nerve stimulation and deep brain stimulation, the available data do not give any evidence for differences in efficacy and safety in older vs. younger patients. [ABSTRACT FROM AUTHOR]

Surgery is an essential treatment option for patients with drug-resistant epilepsy. While most epilepsy patients worldwide live in low- and middle-income countries (LMIC), most of these countries do not have epilepsy surgery, and those that do have surgical epilepsy services lack capacities. The rapidly growing population in LMIC further widens the gap between the number of patients who can potentially benefit from surgery and those who can actually receive it. This makes the initiation of new surgical epilepsy centers in those countries an urgent issue. Epilepsy surgery is feasible in LMIC, even in resource-poor settings, but lack of local expertise is a major obstacle to the introduction of new surgical services. Importantly, expertise deficits can be compensated by collaborating with a well-established epilepsy center for knowledge transfer, skill building and mentoring. Such projects need to be organized in a multidisciplinary team, should focus on the given circumstances, and should use technologies and personnel that are reasonably available and can function sustainably. Local cultural factors and improvement of patients’ quality of life are further spotlights reflected by an increasing number of studies. As a general outline for a new surgical epilepsy program in LMIC, it is recommended to initially focus on patients with mesial temporal lobe epilepsy due to hippocampal sclerosis or other well defined pathologies. These constellations have an excellent surgical outcome in terms of seizure control, can be diagnosed by non-invasive methods, and can be reliably identified even under low-resource conditions. Moreover, surgery can be performed with a highly standardized approach and at reasonable costs, and the vast majority of patients will benefit from surgical intervention. The range of services can then be gradually expanded, depending on growing expertise, local needs, prospects and constraints. Although the introduction of surgical epilepsy services in LMIC can face several challenges, none of them should be a permanent barrier for further establishments. [ABSTRACT FROM AUTHOR]

Background: Epilepsy surgery cases are becoming more complex and increasingly require invasive video-EEG monitoring (VEM) with intracranial subdural or intracerebral electrodes, exposing patients to substantial risks. We assessed the utility and safety of using foramen ovale (FO) and epidural peg electrodes (FOP) as a next step diagnostic approach following scalp VEM. Methods: We analyzed clinical, electrophysiological, and imaging characteristics of 180 consecutive patients that underwent FOP VEM between 1996 and 2021. Multivariate logistic regression was used to assess predictors of clinical and electrophysiological outcomes. Results: FOP VEM allowed for immediate resection recommendation in 36 patients (20.0%) and excluded this option in 85 (47.2%). Fifty-nine (32.8%) patients required additional invasive EEG investigations; however, only eight with bilateral recordings. FOP VEM identified the ictal onset in 137 patients, compared to 96 during prior scalp VEM, p =.004. Predictors for determination of ictal onset were temporal lobe epilepsy (OR 2.9, p =.03) and lesional imaging (OR 3.1, p =.01). Predictors for surgery recommendation were temporal lobe epilepsy (OR 6.8, p <.001), FO seizure onset (OR 6.1, p =.002), and unilateral interictal epileptic activity (OR 3.8, p =.02). One-year postsurgical seizure freedom (53.3% of patients) was predicted by FO ictal onset (OR 5.8, p =.01). Two patients experienced intracerebral bleeding without persisting neurologic sequelae. Conclusion: FOP VEM adds clinically significant electrophysiological information leading to treatment decisions in two-thirds of cases with a good benefit–risk profile. Predictors identified for electrophysiological and clinical outcome can assist in optimally selecting patients for this safe diagnostic approach. [ABSTRACT FROM AUTHOR]

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Copyright of Zeitschrift für Epileptologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Epileptologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: When treating patients with epileptic seizures in the emergency room (ER), it is of paramount importance to rapidly assess whether the seizure was acute symptomatic or unprovoked as the former points to a potentially life-threatening underlying condition. In this study, we seek to identify predictors and analyze characteristics of acute symptomatic seizures (ASS). Methods: Data from patients presenting with seizures to highly frequented ERs of two sites of a university hospital were analyzed retrospectively. Seizures were classified as acute symptomatic or unprovoked according to definitions of the International League Against Epilepsy. Univariate and multivariate analysis were conducted to identify predictors; furthermore, characteristics of ASS were assessed. Results: Finally, 695 patients were included, 24.5% presented with ASS. Variables independently associated with ASS comprised male sex (OR 3.173, 95% CI 1.972–5.104), no prior diagnosis of epilepsy (OR 11.235, 95% CI 7.195–17.537), and bilateral/generalized tonic–clonic seizure semiology (OR 2.982, 95% CI 1.172–7.588). Alcohol withdrawal was the most common cause of ASS (74.1%), with hemorrhagic stroke being the second most prevalent etiology. Neuroimaging was performed more often in patients with the final diagnosis of ASS than in those with unprovoked seizures (82.9% vs. 67.2%, p < 0.001). Patients with ASS were more likely to receive acute antiseizure medication in the ER (55.9% vs. 30.3%, p < 0.001). Conclusions: In one quarter of patients presenting to the ER after an epileptic fit, the seizure had an acute symptomatic genesis. The independently associated variables may help to early identify ASS and initiate management of the underlying condition. [ABSTRACT FROM AUTHOR]

Objective: 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is widely used in presurgical assessment in patients with drug‐resistant focal epilepsy (DRE) if magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) do not localize the seizure onset zone or are discordant. Methods: In this multicenter, retrospective observational cohort study, we included consecutive patients with DRE who had undergone FDG‐PET as part of their presurgical workup. We assessed the utility of FDG‐PET, which was defined as contributing to the decision‐making process to refer for resection or intracranial EEG (iEEG) or to conclude surgery was not feasible. Results: We included 951 patients in this study; 479 had temporal lobe epilepsy (TLE), 219 extratemporal epilepsy (ETLE), and 253 epilepsy of uncertain lobar origin. FDG‐PET showed a distinct hypometabolism in 62% and was concordant with ictal EEG in 74% in TLE and in 56% in ETLE (p <.001). FDG‐PET was useful in presurgical decision‐making in 396 patients (47%) and most beneficial in TLE compared to ETLE (58% vs. 44%, p =.001). Overall, FDG‐PET contributed to recommending resection in 78 cases (20%) and iEEG in 187 cases (47%); in 131 patients (33%), FDG‐PET resulted in a conclusion that resection was not feasible. In TLE, seizure‐freedom 1 year after surgery did not differ significantly (p =.48) between patients with negative MRI and EEG‐PET concordance (n = 30, 65%) and those with positive MRI and concordant EEG (n = 46, 68%). In ETLE, half of patients with negative MRI and EEG‐PET concordance and three quarters with positive MRI and concordant EEG were seizure‐free postsurgery (n = 5 vs. n = 6, p =.28). Significance: This is the largest reported cohort of patients with DRE who received presurgical FDG‐PET, showing that FDG‐PET is a useful diagnostic tool. MRI‐negative and MRI‐positive cases with concordant FDG‐PET results (with either EEG or MRI) had a comparable outcome after surgery. These findings confirm the significance of FDG‐PET in presurgical epilepsy diagnostics. [ABSTRACT FROM AUTHOR]

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Background and Purpose: The KCNQ2 gene encodes for the Kv7.2 subunit of non‐inactivating potassium channels. KCNQ2‐related diseases range from autosomal dominant neonatal self‐limited epilepsy, often caused by KCNQ2 haploinsufficiency, to severe encephalopathies caused by KCNQ2 missense variants. In vivo and in vitro effects of the sodium channel blocker eslicarbazepine acetate (ESL) and eslicarbazepine metabolite (S‐Lic) in a mouse model of self‐limited neonatal epilepsy as a first attempt to assess the utility of ESL in the KCNQ2 disease spectrum was investigated. Experimental Approach Effects of S‐Lic on in vitro physiological and pathological hippocampal neuronal activity in slices from mice carrying a heterozygous deletion of Kcnq2 (Kcnq2+/−) and Kcnq2+/+ mice were investigated. ESL in vivo efficacy was investigated in the 6‐Hz psychomotor seizure model in both Kcnq2+/− and Kcnq2+/+ mice. Key Results: S‐Lic increased the amplitude and decreased the incidence of physiological sharp wave–ripples in a concentration‐dependent manner and slightly decreased gamma oscillations frequency. 4‐Aminopyridine‐evoked seizure‐like events were blocked at high S‐Lic concentrations and substantially reduced in incidence at lower concentrations. These results were not different in Kcnq2+/+ and Kcnq2+/− mice, although the EC50 estimation implicated higher efficacy in Kcnq2+/−animals. In vivo, Kcnq2+/− mice had a lower seizure threshold than Kcnq2+/+ mice. In both genotypes, ESL dose‐dependently displayed protection against seizures. Conclusions and Implications: S‐Lic slightly modulates hippocampal oscillations and blocks epileptic activity in vitro and in vivo. Our results suggest that the increased excitability in Kcnq2+/− mice is effectively targeted by S‐Lic high concentrations, presumably by blocking diverse sodium channel subtypes. [ABSTRACT FROM AUTHOR]

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Background: Electroencephalography (EEG) significantly contributes to the neuroprognostication after resuscitation from cardiac arrest. Recent studies suggest that the prognostic value of EEG is highest for continuous recording within the first days after cardiac arrest. Early continuous EEG, however, is not available in all hospitals. In this observational study, we sought to evaluate the predictive value of a 'late' EEG recording 5–14 days after cardiac arrest without sedatives. Methods: We retrospectively analyzed EEG data in consecutive adult patients treated at the medical intensive care units (ICU) of the Charité—Universitätsmedizin Berlin. Outcome was assessed as cerebral performance category (CPC) at discharge from ICU, with an unfavorable outcome being defined as CPC 4 and 5. Results: In 187 patients, a 'late' EEG recording was performed. Of these patients, 127 were without continuous administration of sedative agents for at least 24 h before the EEG recording. In this patient group, a continuously suppressed background activity < 10 µV predicted an unfavorable outcome with a sensitivity of 31% (95% confidence interval (CI) 20–45) and a specificity of 99% (95% CI 91–100). In patients with suppressed background activity and generalized periodic discharges, sensitivity was 15% (95% CI 7–27) and specificity was 100% (95% CI 94–100). GPDs on unsuppressed background activity were associated with a sensitivity of 42% (95% CI 29–46) and a specificity of 92% (95% CI 82–97). Conclusions: A 'late' EEG performed 5 to 14 days after resuscitation from cardiac arrest can aide in prognosticating functional outcome. A suppressed EEG background activity in this time period indicates poor outcome. [ABSTRACT FROM AUTHOR]

Objectives: In genetic generalized epilepsies (GGE), valproic acid (VPA) is the most efficacious compound. However, due to teratogenicity and increased risk for impaired cognitive development after intrauterine exposure, its use in women of fertile age is strictly regulated but sometimes unavoidable. Methods: All patients with GGE treated at the outpatient clinic of a tertiary epilepsy center with at least one visit between January 2015 and April 2020 were included in this retrospective study. The rate of women aged 18 to 49 years taking VPA was compared to that of men of the same age group and to women > 49 years. Furthermore, in each group, clinical variables associated with VPA use were sought. Results: Twenty‐eight out of 125 women of fertile age (22%) were treated with VPA, compared to 28 out of 56 men ≤ 49 years (50%; p =.002) and to 22 out of 40 female patients > 49 years (55%; p <.001). VPA dose was lower in fertile women compared to men, with no difference in seizure freedom rates. In women ≤ 49 years, multivariate analysis demonstrated age as the only variable independently associated with VPA use (OR 1.095; 95% CI 1.036–1.159). In the other two groups, no associated variables were identified. Conclusions: Despite warnings with respect to teratogenicity and impaired cognitive development with VPA, from 2015 to 2020, almost every fourth women of fertile age with GGE received this compound. Inevitably lower VPA doses in these women seem sufficient for favorable seizure freedom rates. [ABSTRACT FROM AUTHOR]

Objective: In focal epilepsy, data on the etiology‐specific response to antiseizure medication (ASM) are surprisingly sparse. In this study, we sought to reappraise whether seizure outcome of pharmacological treatment is linked to the underlying etiology. Furthermore, we assessed ASM load with respect to the cause of epilepsy. Methods: Data were retrospectively obtained from the electronic database of the three sites of an academic adult epilepsy outpatient clinic. For each patient, presumed cause of epilepsy was categorized into one of nine etiological groups. Individual drug loads were calculated according to the 2020 World Health Organization Center for Drug Statistics Methodology ATC/DDD Index. Univariate and multivariate analyses were conducted to explore the association between different etiologies and outcome regarding 12‐month seizure freedom as well as ASM load. Results: A total of 591 patients with focal epilepsy were included in the final analysis. Ischemic stroke was the etiology with the highest rate of 12‐month terminal seizure freedom (71.2%, 95% confidence interval [CI] = 57.9–82.2) and, considering all etiological groups, was an independent predictor of seizure freedom (odds ratio = 2.093, 95% CI = 1.039–4.216). The lowest rates of seizure freedom were observed in patients with hippocampal sclerosis (28.2%, 95% CI = 15.0–44.9) and malformation of cortical development (16.7%, 95% CI = 2.1–48.4). In patients with ischemic stroke, median ASM load (1.0, interquartile range [IQR] =.5–1.8) was significantly lower compared to that in patients with hippocampal sclerosis (median = 1.8, IQR = 1.2–3.0, p =.008) and brain tumors (median = 1.7, IQR =.7–3.2, p =.049). Significance: Response to treatment with ASM is highly etiology‐specific and best in patients with epilepsy due to ischemic stroke. Interestingly, this most favorable treatment outcome can be achieved by the lowest ASM load considering all etiological groups. In focal epilepsy, etiology should be taken into account when counseling patients about their expected seizure outcome with pharmacological treatment and when tailoring initial ASM doses. [ABSTRACT FROM AUTHOR]

Objectives: To describe incidence, risk factors, and treatment of poststroke epilepsy (PSE) in Germany based on claims data. Methods: Retrospective analysis of claims data from a German public sickness fund (AOK PLUS). Patients with acute stroke hospitalizations from January 01, 2011 and December 31, 2015 (index hospitalization) were followed for 12–72 months. Outcomes included incidence of PSE (patients with ≥2 seizure claims [during/after index hospitalization], or ≥1 seizure claim after index hospitalization), multivariate Cox‐regression analyses of time to seizure claim and death after index stroke hospitalization discharge, and antiepileptic drug (AED) treatment. Results: Among 53 883 patients with stroke (mean follow‐up of 829.05 days [median 749]), 6054 (11.24%) had ≥1 seizure claim (mean age 73.95 years, 54.18% female). 2130 (35.18%) patients had a seizure claim during index hospitalization (indicative of acute symptomatic seizures). Estimated incidence of PSE (cases/1000 patient‐years) was 94.49 within 1 year. Risk of seizure claim following hospital discharge was higher in patients with hemorrhagic stroke (hazard ratio [HR] =1.13; p <.001) vs those with cerebral infarction. Seizure claim during index hospitalization was a risk factor for seizure claims after hospital discharge (HR =6.97; p <.001) and early death (HR =1.78; p <.001). In the first year of follow‐up, AEDs were prescribed in 73.75% of patients with seizure claims. Conclusions: Incidence of PSE was in line with previous studies. Hemorrhagic stroke and seizure claim during index hospitalization were risk factors for seizure claims after hospital discharge. Most patients with seizure claims received AED treatment. [ABSTRACT FROM AUTHOR]

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Objectives: To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video‐EEG monitoring (sca‐VEM), semi‐invasive (sem‐)VEM with foramen ovale and/or peg electrodes, and invasive (in‐)VEM. Methods: Consecutive patients, who underwent presurgical assessment with at least one sca‐VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. Results: Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca‐, 36 sem‐, and 57 in‐VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca‐ or additional sem‐VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in‐VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in‐VEM comprised intellectual disability (OR 4.721, 95% CI 1.047–21.284), extratemporal focal aware non‐motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124–0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100–0.614 and 0.149, 95% CI 0.027–0.829, respectively). Conclusions: During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations. [ABSTRACT FROM AUTHOR]

Epileptiform activity alters gene expression in the central nervous system, a phenomenon that has been studied extensively in animal models. Here, we asked whether also in vitro models of seizures are in principle suitable to investigate changes in gene expression due to epileptiform activity and tested this hypothesis mainly in rodent and additionally in some human brain slices. We focused on three genes relevant for seizures and epilepsy: FOS proto-oncogene (c-Fos), inducible cAMP early repressor (Icer) and mammalian target of rapamycin (mTor). Seizure-like events (SLEs) were induced by 4-aminopyridine (4-AP) in rat entorhinal-hippocampal slices and by 4-AP/8 mM potassium in human temporal lobe slices obtained from surgical treatment of epilepsy. SLEs were monitored simultaneously by extracellular field potentials and intrinsic optical signals (IOS) for 1–4 h, mRNA expression was quantified by real time PCR. In rat slices, both duration of SLE exposure and SLE onset region were associated with increased expression of c-Fos and Icer while no such association was shown for mTor expression. Similar to rat slices, c-FOS induction in human tissue was increased in slices with epileptiform activity. Our results indicate that irrespective of limitations imposed by ex vivo conditions, in vitro models represent a suitable tool to investigate gene expression. Our finding is of relevance for the investigation of human tissue that can only be performed ex vivo. Specifically, it presents an important prerequisite for future studies on transcriptome-wide and cell-specific changes in human tissue with the goal to reveal novel candidates involved in the pathophysiology of epilepsy and possibly other CNS pathologies. [ABSTRACT FROM AUTHOR]

Previous studies have shown that cognitive demands and physical exercise stimulate adult neurogenesis in the dentate gyrus and hippocampus. Recent observations in healthy humans and patients with mild cognitive impairment moreover suggest that training‐induced increases in hippocampal volume may be associated with improved memory performance. The corresponding plasticity processes in hippocampal volume may occur on timescales of months to years. For patients with focal lesions in this region, previous functional imaging studies suggest that increased recruitment of the contralateral hippocampus and extratemporal regions may be an important part of the reorganization of episodic memory. However, it is currently unclear whether focal damage to the medial temporal lobe (MTL) induces gray matter (GM) volume changes in the intact contralateral hippocampus and in connected network regions on a shorter timescale. We therefore investigated whether unilateral resection of the MTL, including the hippocampus, induces measurable volumetric changes in the contralateral hippocampus and in the default mode network (DMN). We recruited 31 patients with unilateral left (N = 19) or right (N = 12) hippocampal sclerosis undergoing MTL resection for treatment of drug‐resistant epilepsy. Structural MRI was acquired immediately before and 3 months after surgery. Longitudinal voxel‐based morphometry (VBM) analysis revealed a significant increase of right hippocampal volume following resection of the left anterior MTL. Furthermore, this patient group showed GM volume increases in the DMN. These results demonstrate significant structural plasticity of the contralateral hippocampus, even in patients with a long‐standing unilateral hippocampal dysfunction and structural reorganization processes extending to distant, but functionally connected brain regions. [ABSTRACT FROM AUTHOR]

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Objective: To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. Methods: Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters. Results: Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention. Conclusions: This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient. [ABSTRACT FROM AUTHOR]

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Background: Once adults with long-standing idiopathic generalised epilepsy have achieved stable seizure remission, patients or physicians may attempt to discontinue their antiepileptic drug treatment. To date, risk of subsequent seizure relapse across the four idiopathic generalised epilepsy syndromes is largely unknown, and so are the clinical variables associated. Methods: For this retrospective observational study, 256 adult outpatients with idiopathic generalised epilepsy were evaluated. Data were obtained from outpatient charts and, if possible, from additional telephone or mail interviews. Results: In 84 patients (33%), antiepileptic medication was discontinued at least once. Median patient age at antiepileptic drug withdrawal was 33 years, and median duration of subsequent follow-up was 20 years. Seizures recurred in 46% of patients after a median latency of 11 months. Following multivariable analysis, seizure relapse was independently associated with short duration of seizure remission beforehand. If medication was withdrawn after < 5 years of seizure freedom, two-thirds of patients had a seizure relapse, while among those in remission for ≥ 5 years, only one-third relapsed. Conclusions: Discontinuation of antiepileptic drug treatment can be successful in every other adult with long-standing idiopathic generalised epilepsy. Short duration of prior seizure remission appears to be a relevant predictor of seizure recurrence. [ABSTRACT FROM AUTHOR]